The Role of the Achiral Template in Enantioselective Transformations. Radical Conjugate Additions to α-Methacrylates Followed by Hydrogen Atom Transfer

Abstract

We have evaluated various achiral templates (1a − g, 10, and 16) in conjunction with chiral Lewis acids in the conjugate addition of nucleophilic radicals to α-methacrylates followed by enantioselective H-atom transfer. Of these, a novel naphthosultam template (10) gave high enantioselectivity in the H-atom-transfer reactions with ee's up to 90%. A chiral Lewis acid derived from MgBr₂ and bisoxazoline (2) gave the highest selectivity in the enantioselective hydrogen-atom-transfer reactions. Non-C₂ symmetric oxazolines (20 − 25) have also been examined as ligands, and of these, compound 25 gave optimal results (87% yield and 80% ee). Insights into rotamer control in α-substituted acrylates and the critical role of the tetrahedral sulfone moiety in realizing high selectivity are discussed.